Antimicrobial and Biophysical Properties of Surfactant Supplemented with an Antimicrobial Peptide for Treatment of Bacterial Pneumonia

Abstract

BACKGROUND: Antibiotic resistant bacterial infections represent an emerging health concern in clinical settings, and a lack of novel developments in the pharmaceutical pipeline is creating a "perfect storm" for multi-drug resistant bacterial infections. Antimicrobial peptides (AMPs) have been suggested as future therapeutics for these drug-resistant bacteria, as they have potent broad spectrum activity, with little development of resistance. Due to the unique structure of the lung, bacterial pneumonia has the additional problem of delivering antimicrobials to the site of infection. One potential solution is co-administration of AMPs with exogenous surfactant, allowing for distribution of the peptides to distal airways, and opening of collapsed lung regions. OBJECTIVE: The objective of this study was to test various surfactant/AMP mixtures with regards to maintaining pulmonary surfactant biophysical properties and bactericidal functions. METHODS: This study compared the properties of four AMPs (CATH-1, CATH-2, CRAMP, LL-37) suspended in exogenous surfactant (BLES) by assessing surfactant/AMP mixture biophysical and antimicrobial functions. Antimicrobial activity was tested against Methillicin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. RESULTS: All AMP/surfactant mixtures exhibited an increase of spreading compared to BLES control. BLES+CATH-2 mixtures had no significantly different minimum surface tension versus BLES control. Compared to the other cathelicidins, CATH-2 retained the most bactericidal activity in the presence of BLES. DISCUSSION: BLES+CATH-2 mixture appears to be an optimal surfactant/AMP mixture based on in vitro assays. Future directions involve investigating the potential of this mixture in animal models of bacterial pneumonia.